PSMB4 (proteasome 20S subunit beta 4)

Gene

• Entrez ID: 5692
• Gene name: Proteasome 20S subunit beta 4
• Gene symbol: PSMB4
• Synonyms: HN3, HsN3, PRAAS3, PROS-26, PROS26
• Chromosome: 1
• Chromosome location: 1q21.3
• Summary: The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs200946642	G>A,T	Pathogenic	5 prime UTR variant
rs1235715459	->G	Pathogenic	Coding sequence variant, frameshift variant
rs1553209362	CTTAGTAGA>-	Pathogenic	Coding sequence variant, inframe deletion
rs1553209373	C>A	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT050351	hsa-miR-25-3p	CLASH	23622248
MIRT1270234	hsa-miR-1261	CLIP-seq
MIRT1270235	hsa-miR-1299	CLIP-seq
MIRT1270236	hsa-miR-3545-3p	CLIP-seq
MIRT1270237	hsa-miR-3973	CLIP-seq
MIRT1270238	hsa-miR-4277	CLIP-seq
MIRT1270239	hsa-miR-4436b-3p	CLIP-seq
MIRT1270240	hsa-miR-4480	CLIP-seq
MIRT1270241	hsa-miR-4662a-5p	CLIP-seq
MIRT1270242	hsa-miR-4699-3p	CLIP-seq
MIRT1270243	hsa-miR-4742-3p	CLIP-seq
MIRT1270244	hsa-miR-4761-3p	CLIP-seq
MIRT1270245	hsa-miR-4782-5p	CLIP-seq
MIRT1270246	hsa-miR-516b	CLIP-seq
MIRT1270247	hsa-miR-520d-5p	CLIP-seq
MIRT1270248	hsa-miR-520g	CLIP-seq
MIRT1270249	hsa-miR-520h	CLIP-seq
MIRT1270250	hsa-miR-524-5p	CLIP-seq
MIRT1270251	hsa-miR-548n	CLIP-seq
MIRT1270252	hsa-miR-548t	CLIP-seq
MIRT1270253	hsa-miR-891b	CLIP-seq
MIRT1270234	hsa-miR-1261	CLIP-seq
MIRT1270235	hsa-miR-1299	CLIP-seq
MIRT1270238	hsa-miR-4277	CLIP-seq
MIRT1270239	hsa-miR-4436b-3p	CLIP-seq
MIRT1270243	hsa-miR-4742-3p	CLIP-seq
MIRT1270244	hsa-miR-4761-3p	CLIP-seq
MIRT1270245	hsa-miR-4782-5p	CLIP-seq
MIRT1270246	hsa-miR-516b	CLIP-seq
MIRT1270253	hsa-miR-891b	CLIP-seq
MIRT1270234	hsa-miR-1261	CLIP-seq
MIRT1270235	hsa-miR-1299	CLIP-seq
MIRT1270238	hsa-miR-4277	CLIP-seq
MIRT1270239	hsa-miR-4436b-3p	CLIP-seq
MIRT1270243	hsa-miR-4742-3p	CLIP-seq
MIRT1270244	hsa-miR-4761-3p	CLIP-seq
MIRT1270245	hsa-miR-4782-5p	CLIP-seq
MIRT1270246	hsa-miR-516b	CLIP-seq
MIRT1270251	hsa-miR-548n	CLIP-seq
MIRT1270253	hsa-miR-891b	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	TAS
GO:0000209	Process	Protein polyubiquitination	TAS
GO:0000502	Component	Proteasome complex	IDA	17323924, 26524591
GO:0001530	Function	Lipopolysaccharide binding	IEA
GO:0002223	Process	Stimulatory C-type lectin receptor signaling pathway	TAS
GO:0002479	Process	Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	TAS
GO:0002862	Process	Negative regulation of inflammatory response to antigenic stimulus	IEA
GO:0004175	Function	Endopeptidase activity	IBA	21873635
GO:0004298	Function	Threonine-type endopeptidase activity	IEA
GO:0005515	Function	Protein binding	IPI	15231748, 17189198, 25416956, 28514442, 32296183, 32814053
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	TAS	16130169
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005739	Component	Mitochondrion	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005839	Component	Proteasome core complex	IBA	21873635
GO:0005839	Component	Proteasome core complex	ISS
GO:0006521	Process	Regulation of cellular amino acid metabolic process	TAS
GO:0010499	Process	Proteasomal ubiquitin-independent protein catabolic process	IBA	21873635
GO:0010972	Process	Negative regulation of G2/M transition of mitotic cell cycle	TAS
GO:0016032	Process	Viral process	IEA
GO:0016579	Process	Protein deubiquitination	TAS
GO:0019774	Component	Proteasome core complex, beta-subunit complex	ISS
GO:0031145	Process	Anaphase-promoting complex-dependent catabolic process	TAS
GO:0031146	Process	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	TAS
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	TAS
GO:0036064	Component	Ciliary basal body	IDA	29257953
GO:0038061	Process	NIK/NF-kappaB signaling	TAS
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IBA	21873635
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	TAS
GO:0043488	Process	Regulation of mRNA stability	TAS
GO:0043687	Process	Post-translational protein modification	TAS
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0055085	Process	Transmembrane transport	TAS
GO:0060071	Process	Wnt signaling pathway, planar cell polarity pathway	TAS
GO:0061418	Process	Regulation of transcription from RNA polymerase II promoter in response to hypoxia	TAS
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0070498	Process	Interleukin-1-mediated signaling pathway	TAS
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	TAS
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	TAS
GO:1901990	Process	Regulation of mitotic cell cycle phase transition	TAS
GO:1902036	Process	Regulation of hematopoietic stem cell differentiation	TAS

Other IDs

• MIM: 602177
• HGNC: 9541
• e!Ensembl: ENSG00000159377

Protein

• UniProt ID: P28070
• Protein name: Proteasome subunit beta type-4 (26 kDa prosomal protein) (HsBPROS26) (PROS-26) (Macropain beta chain) (Multicatalytic endopeptidase complex beta chain) (Proteasome beta chain) (Proteasome chain 3) (HsN3) (Proteasome subunit beta-7) (beta-7)
• Protein function: Non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. As
• PDB: 4R3O, 4R67, 5A0Q, 5GJQ, 5GJR, 5L4G, 5LE5, 5LEX, 5LEY, 5LEZ, 5LF0, 5LF1, 5LF3, 5LF4, 5LF6, 5LF7, 5LN3, 5M32, 5T0C, 5T0G, 5T0H, 5T0I, 5T0J, 5VFO, 5VFP, 5VFQ, 5VFR, 5VFS, 5VFT, 5VFU, 6AVO, 6E5B, 6KWY, 6MSB, 6MSD, 6MSE, 6MSG, 6MSH, 6MSJ, 6MSK, 6R70, 6REY, 6RGQ, 6WJD, 6WJN, 6XMJ, 7AWE, 7B12, 7LXV, 7NAN, 7NAO
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00227	Proteasome	50 → 237	Proteasome subunit	Domain

• Sequence:

  MEAFLGSRSGLWAGGPAPGQFYRIPSTPDSFMDPASALYRGPITRTQNPMVTGTSVLGVK
  FEGGVVIAADMLGSYGSLARFRNISRIMRVNNSTMLGASGDYADFQYLKQVLGQMVIDEE
  LLGDGHSYSPRAIHSWLTRAMYSRRSKMNPLWNTMVIGGYADGESFLGYVDMLGVAYEAP
  SLATGYGAYLAQPLLREVLEKQPVLSQTEARDLVERCMRVLYYRDARSYNRFQIATVTEK
  GVEIEGPLSTETNWDIAHMISGFE

• Sequence length: 264

Pathways

KEGG:

Proteasome
Alzheimer disease
Parkinson disease
Amyotrophic lateral sclerosis
Huntington disease
Spinocerebellar ataxia
Prion disease
Pathways of neurodegeneration - multiple diseases

Reactome:

Activation of NF-kappaB in B cells
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
Cross-presentation of soluble exogenous antigens (endosomes)
Autodegradation of Cdh1 by Cdh1:APC/C
SCF-beta-TrCP mediated degradation of Emi1
APC/C:Cdc20 mediated degradation of Securin
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
Cdc20:Phospho-APC/C mediated degradation of Cyclin A
Vpu mediated degradation of CD4
Vif-mediated degradation of APOBEC3G
SCF(Skp2)-mediated degradation of p27/p21
Degradation of beta-catenin by the destruction complex
Downstream TCR signaling
Separation of Sister Chromatids
FCERI mediated NF-kB activation
Autodegradation of the E3 ubiquitin ligase COP1
Regulation of ornithine decarboxylase (ODC)
ABC-family proteins mediated transport
AUF1 (hnRNP D0) binds and destabilizes mRNA
Asymmetric localization of PCP proteins
Degradation of AXIN
Degradation of DVL
Hedgehog ligand biogenesis
Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
Dectin-1 mediated noncanonical NF-kB signaling
CLEC7A (Dectin-1) signaling
Degradation of GLI1 by the proteasome
GLI3 is processed to GLI3R by the proteasome
Hedgehog 'on' state
Regulation of RAS by GAPs
TNFR2 non-canonical NF-kB pathway
NIK-->noncanonical NF-kB signaling
Defective CFTR causes cystic fibrosis
MAPK6/MAPK4 signaling
UCH proteinases
Ub-specific processing proteases
CDT1 association with the CDC6:ORC:origin complex
Orc1 removal from chromatin
CDK-mediated phosphorylation and removal of Cdc6
G2/M Checkpoints
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A
Ubiquitin-dependent degradation of Cyclin D
The role of GTSE1 in G2/M progression after G2 checkpoint
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
RUNX1 regulates transcription of genes involved in differentiation of HSCs
Regulation of RUNX2 expression and activity
Regulation of RUNX3 expression and activity
Regulation of PTEN stability and activity
Neddylation
Interleukin-1 signaling
Antigen processing: Ubiquitination & Proteasome degradation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Arthritis	Arthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470
Lipodystrophy	Lipodystrophy	rs553668, rs766817317
Myocardial infarction	Myocardial Infarction	rs12316150, rs41303970, rs909253, rs7291467, rs2234693	21211798

Unknown
Disease name	Disease term	dbSNP ID	References
Acanthosis nigricans	Acanthosis Nigricans	rs780668
Conjunctivitis	Conjunctivitis
Lymphopenia	Lymphopenia
Mental depression	Unipolar Depression, Major Depressive Disorder	rs587778876, rs587778877	18504423
Myositis	Myositis
Panniculitis	Panniculitis
Sinusitis	Sinusitis